TITLE:
NPHS2 Gene Mutation and Polymorphisms in Indonesian Children with Steroid-Resistant Nephrotic Syndrome
AUTHORS:
Dedi Rachmadi, Ani Melani, Leo Monnens
KEYWORDS:
Steroid-Resistant Nephrotic Syndrome, NPHS2 Gene, Polymorphism
JOURNAL NAME:
Open Journal of Pediatrics,
Vol.5 No.1,
February
10,
2015
ABSTRACT: Objective:Although several NPHS2 gene mutations
and polymorphisms were described andassociated
with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),theoccurrence
of these genetic abnormalities or variants appearedto be influenced by race and ethnic
group. We have investigatedprobable
mutations and variants in NPHS2 gene involved in SRNS and their association
with clinical manifestations. Methods: We examined 28 childrenwith primary SRNSwhovisitedthe pediatric nephrology division of
10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene
wereconducted through screeningsfor the exon 1, exon 2, and exon 8.
The mutational analysis of NPHS2 was performed by DNA sequencing.Fisher’s Exact Test was used to
determinethecorrelationbetweenNPHS2 polymorphisms and clinical
manifestations.Results:Sevenfemales (25%) and 21 males (75%)participated in the study.The mean age of the subjects with 95%
CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI
is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years
at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11
(39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95%
CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood
pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic
blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.We identified 6 NPHS2polymorphisms,i.e.g.-52G>T, c.101A>G,
g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutationwas found. There wasno correlationbetweenNPHS2 polymorphisms and clinical
manifestations (p > 0.05). Conclusion: Theresults
demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that
were identified have no correlation with the clinical manifestation in
Indonesian children with SRNS.